Regulation of paracellular permeability: factors and mechanisms

Abstract

Epithelial permeability is composed of transcellular permeability and paracellular permeability. Paracellular permeability is controlled by tight junctions (TJs). Claudins and occludin are two major transmembrane proteins in TJs, which directly determine the paracellular permeability to different ions or large molecules. Intracellular signaling pathways including Rho/Rho-associated protein kinase, protein kinase Cs, and mitogen-activated protein kinase, modulate the TJ proteins to affect paracellular permeability in response for diverse stimuli. Cytokines, growth factors and hormones in organism can regulate the paracellular permeability via signaling pathway. The transcellular transporters such as Na-K-ATPase, Na(+)-coupled transporters and chloride channels, can interact with paracellular transport and regulate the TJs. In this review, we summarized the factors affecting paracellular permeability and new progressions of the related mechanism in recent studies, and pointed out further research areas.

Remediation of Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction by Treatment with Diphenyldihaloketones EF24 and CLEFMA

“…The claudins and occludins are two major transmembrane proteins that interact with ZO proteins and directly determine the paracellular permeability to different ions and large molecules (Hu et al, 2013). The function of claudins in epithelial barrier is also subject to modulation by Ser/Thr phosphorylation and interaction with PDZ-binding domains (Groschwitz and Hogan, 2009).…”

Heat Stress and Gut Health in Broilers: Role of Tight Junction Proteins

“…16 As multi-protein complexes, TJ not only hold cells together, but they form channels allowing the transport of substances across the epithelium. 17 Interestingly, the molecular composition, ultrastructure, and function of TJ is regulated by intracellular proteins through a series of intracellular signaling pathways that includes myosin light kinase (MLCK), mitogen-activated protein kinases (MAPK), protein kinase C (PKC) among others.…”

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…The passing of molecules occurs through passive or facilitated diffusion, (active) carrier mediated or paracellular transport [87,88]. Lipophile, large and relatively uncharged drugs are moved transcellularly through cell membranes.…”